Limitation of myocardial infarct size and preservation of left ventricular function by early administration of APSAC in myocardial infarction

Abstract

In cases of acute myocardial infarction (MI), it has been shown that preserving left ventricular function and limiting infarct size with early reperfusion of the occluded artery by means of a thrombolytic agent could eventually result in a reduced mortality rate. The aim of the APSIM study (anisoylated plasminogen steptokinase activator complex [APSAC] dans l'Infarctus du Myocarde) was to demonstrate that early administration of APSAC in patients with recent acute MI could limit the infarct size and preserve left ventricular systolic function. In all, 231 patients with a first acute MI were randomly allocated to either APSAC (30 U over 5 minutes) or to conventional heparin therapy (5,000 IU in bolus injection) within 5 hours of the onset of symptoms. Of these patients, 112 received APSAC and 119 received heparin within a mean period of 188 ± 62 minutes after the onset of symptoms. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p < 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC than in the heparin group. This was true for the entire population (0.53 ± 0.13 vs 0.47 ± 0.13, p = 0.002) as well as for the subgroups of anterior and inferior wall infarctions (0.47 ± 0.13 vs 0.4 ± 0.16, p = 0.004 and 0.56 ± 0.11 vs 0.51 ± 0.09, p = 0.02). At 3 weeks, the difference remained significant for patients with anterior MI. A significant 31% reduction of infarct size was found in the APSAC group (33% for the anterior wall infarction [p < 0.05] and 16% for the interior wall infarction, which was not significant). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = −0.73, p < 0.01). At the end of the 3-week follow-up period, 7 patients in the APSAC and 6 patients in the heparin group had died. In conclusion, the early infusion of APSAC in patients with acute MI produced a high early patency rate, significantly limited the infarct size, and substantially preserved left ventricular systolic function, mainly in the anterior wall infarctions.